Perivascular tissue of internal thoracic artery releases potent nitric oxide and prostacyclin-independent anticontractile factor☆

OBJECTIVE: It has been recently suggested that perivascular tissue (PVT) releases hypothetic adipocyte- or adventitia-derived relaxing factor. The aim of the study was to assess anticontractile properties of perivascular tissue of human internal thoracic artery (ITA) and to check if this activity is nitric oxide (NO)- or prostacyclin-dependent. We also analyzed the influence of pleural adipose tissue on ITA reactivity. METHODS: Human ITA rings were studied in vitro. First, skeletonized and pedicled ITA reactivity to serotonin and angiotensin II was compared. In subsequent experiments fragments of ITA were skeletonized and divided into two preparations. One was incubated alone, the other together with PVT or pleural adipose tissue floating freely in the bath. First, concentration-response curves to either serotonin or angiotensin II were constructed. Tissue was then transferred from one bath to the other and concentration-response curves were reconstructed. The same protocol was applied with the inhibition of NO synthase with L-NMMA (10(-4)M) and cyclooxygenase with indomethacin (10(-5)M). RESULTS: Skeletonization augmented contractile response to serotonin (E(max) 16.6+/-1.85 mN vs 43.8+/-3.87 mN; pedicled vs skeletonized ITA, respectively; p<0.001) and angiotensin II (E(max) 10.9+/-1.07 mN vs 26.6+/-1.45 mN, respectively; p<0.001). PVT presence in the bath caused decrease of E(max) from 40.8+/-5.01 to 20.1+/-2.69 mN for serotonin; p<0.001 and from 31.4+/-3.75 to 13.0+/-1.60 mN for angiotensin II, p<0.001 (PVT(-) vs PVT(+), respectively). PVT did not change ITA sensitivity (EC(50)) to serotonin or angiotensin II. Pleural adipose tissue did not change the contractile response of ITA to serotonin (E(max) 37.2+/-4.95 mN vs 36.3+/-4.83 mN, pleural fat+and pleural fat-, respectively; p=0.9). NO and prostacyclin inhibition failed to abolish anticontractile properties of perivascular tissue. PVT with cyclooxygenase and NO synthase inhibition decreased E(max) of serotonin from 46.6+/-3.03 to 28.2+/-4.02 mN, p<0.001 and E(max) of angiotensin II from 27.2+/-2.00 to 16.4+/-2.10 mN, p<0.001. CONCLUSIONS: Perivascular tissue of ITA releases potent, soluble, nitric oxide and prostacyclin-independent anticontractile factor. The pleural adipose tissue does not influence ITA reactivity to vasoconstrictors. Preservation of perivascular tissue may protect against vasospasm of ITA graft in clinical settings.